Lifeboat Foundation

Microtubule cytoskeletons are highly dynamic cellular components that reorganise during the cell cycle.

Microtubule organization and reorganization during the cell cycle are achieved by regulation of the number, distribution and activity of microtubule-organizing centres (MTOCs). In fission yeast, the Mto1/2 complex determines the activity and distribution of cytoplasmic MTOCs. Upon mitosis, cytoplasmic microtubule nucleation ceases; inactivation of the Mto1/2 complex is triggered by Mto2 hyperphosphorylation. However, the protein kinase(s) that phosphorylates Mto2 remains elusive. Here we show that a conserved signalling network, called MOR (morphogenesis Orb6 network) in fission yeast, negatively regulates cytoplasmic MTOCs through Mto2 phosphorylation to ensure proper microtubule organization. Inactivation of Orb6 kinase, the most downstream MOR component, by attenuation of MOR signalling leads to reduced Mto2 phosphorylation, coincident with increased number of both Mto2 puncta and cytoplasmic microtubules. These defects cause the emergence of uncoordinated mitotic cells with cytoplasmic microtubules, resulting in reduced spindle assembly. Thus, the regulation of Mto2 by the MOR is crucial for cytoplasmic microtubule organization and contributes to reorganization of the microtubule cytoskeletons during the cell cycle.

Microtubules are essential for many cellular processes, such as intracellular transport of proteins and organelles, establishment of cell polarity, cell motility and chromosome segregation [1– 5]. In order to facilitate these different processes at appropriate times during the cell cycle and cell differentiation, microtubules are organized into specific arrangements by microtubule-organizing centres (MTOCs) [2, 4, 5]. For instance, in most eukaryotic cells, the MTOC(s) forms polarized microtubule arrays during interphase and these arrays undergo reorganization to form the bipolar spindle in mitosis. This reorganization proceeds rapidly and precisely during the transition between interphase and mitosis and vice versa. However, the regulation mechanisms coupling cytoskeletal changes with the cell cycle are poorly understood.

The fission yeast Schizosaccharomyces pombe is an excellent model system in which to study cell cycle-dependent microtubule organization by distinct types of MTOCs: the centrosomal MTOC (spindle pole body, SPB) and non-centrosomal MTOCs (interphase MTOC: iMTOC; and equatorial MTOC: eMTOC) [6,7]. During interphase, cytoplasmic microtubules are nucleated from the cytoplasmic face of the SPB, nuclear membrane bound iMTOCs, and pre-existing microtubules to organize a longitudinal array of two to five microtubule bundles [6,7]. During the transition period from interphase to mitosis, nucleation of cytoplasmic microtubules from the iMTOCs ceases and simultaneously intranuclear mitotic spindle microtubules start nucleating from the nucleoplasmic face of the SPB [6,7].

Lymphedema is a chronic condition that affects many cancer survivors. It’s swelling caused by a buildup of lymph fluid, often as a result of cancer treatment. While it can’t be prevented, treatment can help to relieve swelling and improve the ability to function day to day.

Lymphedema is a side effect of some cancer treatments. Learn about symptoms and ways you can manage and treat swelling in your arm or leg caused by

🧠🔬💡

A significant reduction of GABA and monoamine oxidase B (MOAB), the latter of which is an astrocytic enzyme that produces GABA, was also observed in Crym KO mice. These observations suggest that increased synaptic excitation from IOFC terminals leads to lower levels of tonic GABA, which causes reduced presynaptic inhibition.

Study significance

Continue reading “Key brain cells linked to repetitive behaviors in psychiatric diseases” »

Durable remission was achieved with front-line dasatinib plus blinatumomab in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.

NEJM Journal Watch reviews over 250 scientific and medical journals to present important clinical research findings and insightful commentary.

A research team led by the Paul Scherrer Institute has spectroscopically observed the fractionalization of electronic charge in an iron-based metallic ferromagnet. Experimental observation of the phenomenon is not only of fundamental importance. Since it appears in an alloy of common metals at accessible temperatures, it holds potential for future exploitation in electronic devices. The discovery is published in the journal Nature.

Basic quantum mechanics tells us that the fundamental unit of charge is unbreakable: the electron charge is quantized. Yet, we have come to understand that exceptions exist. In some situations, electrons arrange themselves collectively as if they were split into independent entities, each possessing a fraction of the charge.

The fact that charge can be fractionalized is not new: it has been observed experimentally since the early 1980s with the Fractional Quantum Hall Effect. In this, the conductance of a system in which electrons are confined to a two-dimensional plane is observed to be quantized in fractional—rather than integer—units of charge.

Scientists have revealed surprising parallels between aging and schizophrenia. There seem to be similar patterns of gene activity in the brains of people who are aging, and in those with schizophrenia. The same mechanisms may underlie the cognitive disruptions seen in older adults and people with schizophrenia. The findings have been reported in Nature.

In this work, the researchers analyzed gene expression at the single-cell level in post-mortem brain samples from 94 people with schizophrenia and 97 unaffected individuals. This gene activity was altered in two types of cells found in the brain, both neurons and astrocytes. In all, 1.2 million cells from were analyzed. This showed that in neurons, expression changed in genes that are associated with portions of synapses, the space where neurons meet and communicate; and in astrocytes, in genes that are related to synaptic function.

For decades, scientists and pathologists have tried, without much success, to come up with a way to determine which individual lung cancer patients are at greatest risk of having their illness spread, or metastasize, to other parts of the body.

Now a team of scientists from Caltech and the Washington University School of Medicine in St. Louis has fed that problem to artificial intelligence (AI) algorithms, asking computers to predict which cancer cases are likely to metastasize. In a novel pilot study of non-small cell lung cancer (NSCLC) patients, AI outperformed expert pathologists in making such predictions.

These predictions about the progression of lung cancer have important implications in terms of an individual patient’s life. Physicians treating early-stage NSCLC patients face the extremely difficult decision of whether to intervene with expensive, toxic treatments, such as chemotherapy or radiation, after a patient undergoes lung surgery. In some ways, this is the more cautious path because more than half of stage I–III NSCLC patients eventually experience metastasis to the brain. But that means many others do not. For those patients, such difficult treatments are wholly unnecessary.

Colchicine reduced cardiovascular events in patients with diabetes and recent myocardial infarction in a randomized study.

NEJM Journal Watch reviews over 250 scientific and medical journals to present important clinical research findings and insightful commentary.

A Tufts School of Medicine researcher is developing a test to predict lung cancer risk more accurately and reduce the number of scans to detect the condition.